New Insights Into Cryptococcus Spp. Biology and Cryptococcal Meningitis
Purpose of Review
Defective cell–mediated immunity is a major risk factor for cryptococcosis, a fatal disease if untreated. Cryptococcal meningitis (CM), the main presentation of disseminated disease, occurs through hematogenous spread to the brain from primary pulmonary foci, facilitated by yeast virulence factors. We revisit remarkable recent improvements in the prevention, diagnosis and management of CM.
Cryptococcal antigen (CrAg), main capsular polysaccharide of Cryptococcus spp. is detectable in blood and cerebrospinal fluid of infected patients with point of care lateral flow assays. Recent World Health Organization guidelines recommend 7-day amphotericin B plus flucytosine, then 7-day high dose (1200 mg/day) fluconazole for induction treatment of HIV-associated CM. Management of raised intracranial pressure, a consequence of CM, should rely mainly on daily therapeutic lumbar punctures until normalisation. In HIV-associated CM, following introduction of antifungal therapy, (re)initiation of antiretroviral therapy should be delayed by 4–6 weeks to prevent immune reconstitution inflammatory syndrome, common in CM.
CM is a fatal disease whose diagnosis has recently been simplified. Treatment should always include antifungal combination therapy and management of raised intracranial pressure. Screening for immune deficiency should be mandatory in all patients with cryptococcosis.
KeywordsCryptococcus Cryptococcal antigen Lateral flow assay Intracranial pressure Induction therapy
The authors wish to thank Dr. John C.M. Brust for providing the full review of this article.
Compliance with Ethical Standards
Conflict of Interest
Elvis Temfack, David Lawrence, Sarah Delliere, Angela Loyse each declare no potential conflicts of interest. Alexandre Alanio reports personal fees (Educational symposium) from Gilead sciences, outside the submitted work. Fanny Lanternier reports personal fees from Gilead, and from Basilea, outside the submitted work. Olivier Lortholary reports personal fees (Speaker during congresses) from Gilead, Merck, Pfizer, Astellas, outside the submitted work. Timothée Boyer-Chammard reports personal fees (Educational symposium) from Gilead Science, outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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